Pt. III: THE GENES OF
CANCER
Oncogenes & Tumor Suppressor
Genes
Some material in this slideshow comes from http://www.cancer.org
The American Cancer Society
Cancer Genes
• A small subset of genes are particularly
important in the development of cancer.
• Proto-oncogenes (or Oncogenes): whose
proteins stimulate cell division.
• Tumor Suppressor Genes: whose protein
can directly or indirectly prevent cell
division or lead to cell death.
What Are Oncogenes?
• Oncogenes: mutated forms of proto-oncogenes genes
• Cause normal cells to grow out of control and become
cancer cells.
• Proto-oncogenes are the genes that normally control
how often a cell divides and the degree to which it
differentiates (or specializes).
• When a proto-oncogene mutates into an oncogene, it
becomes permanently "turned on" or activated when it
is not supposed to be. When this occurs, the cell
divides too quickly, which can lead to cancer.
• More than 100 oncogenes are now recognized
5 Classes of Oncogenes
• Growth factors: produce proteins that
stimulate cells to grow.
• Growth factor receptors: Genes
amplification causes these proteins to be
overproduced. Extra copies of these genes
results in too many growth factor receptor
molecules in the cell membrane. The cell
becomes overly sensitive to growth-
promoting signals.
5 Classes of Oncogenes (con’t)
• Signal transducers: Protein pathways between the
growth factor receptor and the cell nucleus where the
signal is received. When they are abnormal in cancer
cells, they are turned on.
• Transcription factors: These are the final molecules
in the chain that tell the cell to divide. These
molecules act on the DNA and control which genes
are active in producing RNA and protein.
• Programmed cell death regulators: These
molecules prevent a cell from committing suicide
when it becomes abnormal. When these genes are
overactive they prevent the cell from going through
the suicide process. This leads to an overgrowth of
abnormal cells, which can then become cancerous.
Proto-oncogenes
What Are Tumor Suppressor
Genes?
• Tumor suppressor genes are normal genes that
slow down cell division, repair DNA mistakes,
and tell cells when to die (a process known as
apoptosis or programmed cell death).
• When tumor suppressor genes don’t work
properly, cells can grow out of control, which can
lead to cancer.
• About 30 tumor suppressor genes have been
identified, including p53, BRCA1, BRCA2, APC,
and RB1.
The Difference
• Oncogenes result from the activation (turning
on) of proto-oncogenes
• Tumor suppressor genes cause cancer when
they are inactivated (turned off).
• Another major difference is that while the
overwhelming majority of oncogenes develop
from mutations in normal genes (proto-
oncogenes) during the life of the individual
(acquired mutations), abnormalities of tumor
suppressor genes can be inherited as well as
acquired.
Types of Tumor Suppressor Genes
• Genes that control cell division: Some
tumor suppressor genes help control cell
growth and reproduction.
• Genes that repair DNA: A second group of
tumor suppressor genes is responsible for
repairing DNA damage. Copying errors
occur during DNA replication DNA repair
genes make proteins that proofread DNA
and fix it.
Types of Tumor Suppressor Genes
(con’t)
• Cell "suicide" genes: When DNA become
irreparable the p53 tumor suppressor gene is
responsible for destroying the cell.
– Called programmed cell death or apoptosis.
– If the p53 gene is mutated, cells with DNA
damage avoid death, continue to reproduce & can
eventually become cancerous.
– Mutations in p53 gene can be inherited or
Sporadic